Preferred Label : Growth factors, combined defect of;
Type : Other, mainly phenotypes with suspected mendelian basis;
Alternative titles and symbols : Insulin, insulin-like growth factor I, and epidermal growth factor deficiency; Werner-like syndrome due to combined growth factor deficiency;
Description : In 3 brothers born of healthy nonconsanguineous parents, Hoepffner et al. (1989) demonstrated
a similar clinical phenotype with reduced subcutaneous fat on the limbs, lipodystrophy
in the face and trunk, and reduced relative body weight. The neurocranium was relatively
broad. The face was birdlike, with a beaked nose, moderate micrognathia, and a very
narrow mouth. Other signs were contractures of joints, slight pectus excavatum, flat
feet, and scleroderma-like changes in the skin, which was taut, thin, and atrophic,
with moderate hyperkeratosis of the plantae surfaces and yellowish spotted discolorations
with pigmented areas on the limbs and trunk. The eldest brother, born in 1965, showed
insulin-resistant diabetes mellitus, amenable to diet, and type IV hyperlipoproteinemia
(144600). The parents and the 2 younger brothers showed no disturbance in carbohydrate
or fat metabolism. The microscopic changes in the skin were described by Mensing et
al. (1982), who referred to the condition as a Werner-syndrome-like disorder. Biochemically,
Hoepffner et al. (1989) demonstrated a combined defect in the action of 3 related
peptides, insulin (176730), insulin-like growth factor I (147440) and epidermal growth
factor (131530). Cultured fibroblasts showed a markedly reduced stimulation of RNA
synthesis by the 3 growth factors and a decreased insulin stimulation of 2-deoxy-D-glucose
uptake as compared with normal controls. Receptor binding of the 3 peptides occurred
with normal capacity and affinity. Hoepffner et al. (1989) interpreted the findings
as indicating that signal transfer of the different growth factors has a common denominator
at the postreceptor level and that this is the site of the mutation. The defect may
be located distal to the receptor-associated tyrosine kinases. *FIELD* RF 1. Hoepffner,
H. J.; Dreyer, M.; Reimers, U.; Schmidt-Preuss, U.; Koepp, H. P.; Rudiger, H. W.:
A new familial syndrome with impaired function of three related peptide growth factors.
Hum. Genet. 83: 209-216, 1989. 2. Mensing, H.; Schaeg, G.; Burck, U.; Meigel, W.:
Werner-Syndromartige Erkrankung bei drei Brudern--Beitrag zur Differential-diagnose
der Voralterungssyndrome. Hautarzt 33: 542-547, 1982. *FIELD* CS Limbs: Reduced subcutaneous
fat; Joint contractures; Flat feet Misc: Lipodystrophy of face and trunk;
Inheritance : Autosomal recessive;
Prefixed ID : 233805;
Origin ID : 233805;
UMLS CUI : C2931279;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
